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Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma.

ABSTRACT: Metastatic urothelial cancer is an aggressive disease associated with a poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. After failure of platinum-based therapy and in cisplatin-ineligible patients, therapeutic options are limited. Malignant cells evolve mechanisms to evade immune recognition, including the expression of cell-surface molecules, named immune checkpoints, on tumor and tumor-specific lymphocytes. Immunotherapy, by targeting these checkpoints, represents a new tool to improve the patient outcome in advanced urothelial carcinoma (UC). Recently, the US FDA approved, in a short time, several immune checkpoint inhibitors in metastatic UC, both after failure of platinum-based therapy and in first-line setting in cisplatin-ineligible patients. This article aims to review the place of immunotherapy in advanced UC.

SUBMITTER: Seront E

PROVIDER: S-EPMC6234462 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma.

Seront Emmanuel E Catala Gaëtan G Dermine Alexandre A Lejeune Sarah S Rysselinck Stephane S

Future science OA 20181004 10

Metastatic urothelial cancer is an aggressive disease associated with a poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. After failure of platinum-based therapy and in cisplatin-ineligible patients, therapeutic options are limited. Malignant cells evolve mechanisms to evade immune recognition, including the expression of cell-surface molecules, named immune checkpoints, on tumor and tumor-specific lymphocytes. Immunothe ...[more]

PMID: 30457576

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Project description:BackgroundSeveral immune checkpoint inhibitors (ICIs) are approved for the treatment of advanced urothelial carcinoma (UC). There are limited biomarkers for ICI-treated patients with UC. We investigated the association between body composition and clinical outcomes in ICI-treated UC patients.Materials and methodsWe conducted a retrospective analysis of 70 ICI-treated patients with advanced UC at Winship Cancer Institute from 2015 to 2020. Baseline computed tomography images within 2 months of ICI initiation were collected at mid-L3 and muscle and fat compartments (subcutaneous, intermuscular, and visceral) were segmented using SliceOMatic v5.0 (TomoVision, Magog, Canada). A prognostic body composition risk score (high: 0-1, intermediate: 2-3, or low-risk: 4) was created based on the β coefficient from the multivariate Cox model (MVA) following best-subset variable selection. Our body composition risk score was skeletal muscle index (SMI) + 2 × attenuated skeletal muscle (SM) mean + visceral fat index (VFI). Concordance statistics (C-statistics) were used to quantify the discriminatory magnitude of the predictive model.ResultsMost patients (70%) were men and the majority received ICIs in the second- (46%) or third-line (21%) setting. High-risk patients had significantly shorter overall survival (OS; hazard ratio [HR], 6.72; p < .001), progression-free survival (HR, 5.82; p < .001), and lower chance of clinical benefit (odds ratio [OR], 0.02; p = .003) compared with the low-risk group in MVA. The C-statistics for our body composition risk group and myosteatosis analyses were higher than body mass index for all clinical outcomes.ConclusionBody composition variables such as SMI, SM mean, and VFI may be prognostic and predictive of clinical outcomes in ICI-treated patients with UC. Larger, prospective studies are warranted to validate this hypothesis-generating data.Implications for practiceThis study developed a prognostic body composition risk scoring system using radiographic biomarkers for patients with bladder cancer treated with immunotherapy. The study found that the high-risk patients had significantly worse clinical outcomes. Notably, the study's model was better at predicting outcomes than body mass index. Importantly, these results suggest that radiographic measures of body composition should be considered for inclusion in updated prognostic models for patients with urothelial carcinoma treated with immunotherapy. These findings are useful for practicing oncologists in the academic or community setting, particularly given that baseline imaging is routine for patients starting on treatment with immunotherapy.

Dataset Information

Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma.

Publications

Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma.

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